Up-regulation of NK cell function against head and neck cancer in response to ss-isRNA requires TLR7.
Natural killer (NK) cells play a crucial role in innate immunity as effectors against tumor and pathogen-infected cells. NK-mediated host defense against tumor cells is strongly impaired in patients with head and neck squamous cell carcinoma (HNSCC). Tumor secretion of various immune suppressive mediators contributes to massively compromised immune functions. Herein we demonstrate that NK cell cytotoxicity against tumor cells of HNSCC can be efficiently stimulated by single-stranded immunostimulatory RNA (ss-isRNA). Stimulation with ss-isRNA results in an increased production of interferon-gamma and effector proteins perforin and granzyme B. Our investigations revealed that supernatants of permanent HNSCC cell lines negatively affect the ss-isRNA-triggered stimulation of cytolytic NK cell functions. Stimulation of cytotoxicity requires toll-like receptor 7 (TLR7). Increased expression of NK cell TLR7 was shown in response to ss-isRNA. These results suggest ss-isRNA as a potential immunostimulatory tool of human NK cells against HNSCC.
Pries
Ralph
R
Department of Otorhinolaryngology, University of Schleswig-Holstein Campus Lübeck, D-23538 Lübeck, Germany.
Wulff
Sandra
S
Kesselring
Rebecca
R
Börngen
Kirsten
K
Xie
Lei
L
Wollenberg
Barbara
B
D000276:Adjuvants, Immunologic; D000293:Adolescent; D000328:Adult; D000368:Aged; D002294:Carcinoma, Squamous Cell / Q000201:enzymology / Q000276:immunology / Q000628:therapy*; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D017077:Culture Media, Conditioned / Q000378:metabolism; D003602:Cytotoxicity, Immunologic; D005260:Female; D053804:Granzymes / Q000378:metabolism; D006258:Head and Neck Neoplasms / Q000201:enzymology / Q000276:immunology / Q000628:therapy*; D006801:Humans; D007113:Immunity, Innate; D007371:Interferon-gamma / Q000378:metabolism; D007694:Killer Cells, Natural / Q000201:enzymology / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D054353:Perforin / Q000378:metabolism; D012313:RNA / Q000276:immunology*; D051199:Toll-Like Receptor 7 / Q000378:metabolism*; D015854:Up-Regulation; D055815:Young Adult
D000276:Adjuvants, Immunologic; D017077:Culture Media, Conditioned; C495348:TLR7 protein, human; D051199:Toll-Like Receptor 7; D054353:Perforin; D012313:RNA; D007371:Interferon-gamma; C509213:GZMB protein, human; D053804:Granzymes